ALTERATION OF ACETALDEHYDE METABOLISM IN CARBON TETRACHLORIDE-INTOXICATED RAT LIVER: ANALYSIS USING LIVER PERFUSION SYSTEM

The hepatic metabolism of acetaldehyde in carbon tetrachloride(CCl₄)-intoxicated rats was studied using a non-recirculatinghaemoglobin-free liver-perfusion system. Acetaldehyde uptakeby the liver from acutely CCl₄-treated animals (4.16 mmol/kg,i.p.) at 24 hr after the treatment was not significantly altered,whereas that by the liver from chronically CCl₄-treated animals(2.08 mmol/kg,i.p., twice a week, for 8–12 weeks) wasdecreased by approximately 50% when it was determined in thepresence of 0.01–5 mM acetaldehyde. In liver from ratschronically intoxicated with CCl₄, the following important biochemicalchanges were observed: (1) The activity of low K_m aldehyde dehydrogenase(ALDH) in hepatic mitochondria was decreased by approximately75%. (2) The basal levels of the lactate/pyruvate (cytosolic[NADH]/[NAD⁺]) ratio as well as the ß-hydroxybutyrate/acetoacetate(mitochondrial [NADH]/[NAD⁺]) ratio were elevated by more than2-fold. (3) Mitochondrial NADH oxidation was also reduced byapproximately 35% of the control level. (4) The basal levelof hepatic oxygen uptake was attenuated by approximately 50%,and the infusion of acetaldehyde (0.01–5.0 mM) causeda further decrease in the uptake. (5) The rate of ethanol productionfrom acetaldehyde by the catalytic action of alcohol dehydrogenasewas found to be unaltered when low concentrations of acetaldehyde(0.01–0.2 mM) were used, whereas a significant suppressionof the rate of ethanol production was detected in the presenceof high concentrations of acetaldehyde (0.6–5 mM). Thesedata suggest that the changes in activity of the lowK_m mitochondrialacetaldehyde dehydrogenase and those in mitochondrial NADH oxidationcoupled with mitochondrial respiration may, at least in part,play important roles in the decreased hepatic acetaldehyde metabolismobserved in chronically CCl₄-treated rats.     

Life‐threatening hemorrhage and prolonged wound healing are remarkable phenotypes manifested by complete plasminogen activator inhibitor‐1 deficiency in humans

Summary. Background: Plasminogen activator inhibitor‐1 (PAI‐1) is the primary physiological regulator of urokinase plasminogen activator (uPA) and tissue plasminogen activator (tPA) activity. A number of studies have shown that elevated levels of PAI‐1 are related to pathological states such as an increased risk of arterial thrombotic events and a poor prognosis for cancer patients; however, there are few reports about PAI‐1 deficiency in humans because the disorder is very rare. Objective: To understand the in vivo impact of a complete PAI‐1 deficiency, Serpine1^?/? mice were generated; a number of in vivo studies have been conducted to elucidate the function of PAI‐1 using Serpine1^?/? mice. The phenotypes demonstrated in Serpine1^?/? mice, however, were quite different from those in humans. Therefore, it is necessary to find out and analyze SERPINE1 deficiency in humans. Patient and methods: The patient is a 47‐year‐old woman who has had multiple episodes of major bleeding. Although most of the patient’s blood coagulation factors were functionally normal, her PAI‐1 antigen levels were undetectable. Therefore, DNA sequencing of the SERPINE1 gene were analyzed. Results: The proband had a homozygous 1‐bp duplication (C) at exon 3 (c.356dupC; p.Ile120AspfsX42). Both wild‐type PAI‐1 (42.7 kDa) and mutated (Mut) PAI‐1 (14.7 kDa) were expressed in COS‐1 cells, although the level of Mut PAI‐1 expressed in the cell lysates was much lower. Wild‐type PAI‐1 was observed in the culture supernatant, whereas no Mut PAI‐1 was detected in the supernatant. Conclusions: Considering the results of the present study, the translation of mouse studies to humans must be performed with great care.     

Usefulness of oblique transparent cylinders in facilitating colonoscopy

Recently, the usefulness of the oblique transparent cylinder (OTC) in colonoscopy has been reported. In this study, the efficacy of two newly designed OTCs was evaluated. Colonoscopy performed by six experienced endoscopists in 1005 cases and by one inexperienced endoscopist in 177 cases was analyzed. Short (S) and ultra short (US) cylinders, shorter in length than a conventional long (L) cylinder, were used. The use of OTCs in colonoscopy contributed to a significantly faster insertion into the cecum. The average time to reach the cecum for experienced endoscopists were 12.4 ± 0.3 min without a cylinder, 9.0 ± 0.3 min with a US cylinder, 8.5 ± 0.4 min with an S cylinder and 6.9 ± 0.8 min with an L cylinder, respectively. The visual field and handling of the endoscope were more improved with the S cylinder than the conventional L cylinder. On the other hand, with the L cylinder, the success rate of one inexperienced endoscopist for total colonoscopy reached more than 90% and mean insertion time to reach the cecum was 16.4 ± 1.8 min 7‐months later. Both the success rate and average insertion time for the inexperienced endoscopist were satisfactory considering the rather short learning period. The OTCs were effective in reducing the insertion time. The use of the S cylinder overcame some of the disadvantages of the L cylinder; however, the L cylinder was helpful in improving the technique of an inexperienced endoscopist.     

Analysis of the circumstances at the end of life in children with cancer: A single institution''s experience in Japan

BACKGROUND: With the aim of improving the quality of life of children with cancer, this study presents an analysis of one hospital's experience with terminal care. METHODS: Between 1994 and 2000, 28 children died after treatment for cancer at Hamamatsu University Hospital. The circumstances of their deaths were analyzed through medical records and interviews with 8 sets of bereaved parents. We compared results of this analysis with our previous data collected from 1978 to 1993. RESULTS: Of the 28 children, 11 had leukemia/lymphoma (LL group) and 17 had solid tumors (ST group). Six children (21.4%), all of whom were in the LL group, died of treatment-related complications. Twenty children (71.4%) died during terminal care: three (27.3%) were in the LL group and 17 (100%) in the ST group. Eleven children (39.3%) received terminal care at home and eight (28.6%) of these died at home. The number of children who received terminal care and died at home had increased in comparison with the previous period. Among problems with terminal care identified by parents were the lack of opportunity for the child to continue with education and an inadequate support system after the child's death. CONCLUSIONS: Some advances in the quality of life of the children were recognized. However, these advances were extended to a greater percentage of children in the ST group than in the LL group. The psychosocial problems faced by children and their families are now changing for the better.     

Case report: Portal-systemic encephalopathy due to a congenital extrahepatic portosystemic shunt

We present a case of portal-systemic encephalopathy due to a congenital splenorenal shunt. A 69 year old woman was admitted to hospital because of recurrent episodes of disturbed consciousness. The present episode had begun 3 months prior to admission. Although the patient demonstrated mildly slurred speech, the remainder of her neurological examination was unremarkable. She showed no clinical signs of portal hypertension and her liver function, except for a serum hepaplastin test of 58% and an ICG retention rate of 28% at 15 min, was normal. Her serum ammonium level was 210 μg/dL. The venous phase of a superior mesenteric arteriogram revealed a splenorenal shunt and narrowing of the portal vein, which was 4 mm in diameter. The histological findings, demonstrated by a needle liver biopsy specimen, were consistent with mild fibrosis and lymphocytic infiltration. Following the diagnosis of a splenorenal shunt in the absence of liver cirrhosis, ligature of the shunt was performed with a splenectomy. The portal vein pressure after ligature of the shunt rose from 12.5 to 18.8 mmHg. This shunt was thought to be of congenital origin. The high preoperative serum ammonia concentration decreased to the normal range postoperatively and the serum hepaplastin test and ICG retention rate similarly improved postoperatively. A follow-up superior mesenteric arteriogram was performed during the venous phase, demonstrating resolution of the shunt and decreased portal vein narrowing. The patient has suffered no further episodes of disturbed consciousness postoperatively.     

GLOMERULONEPHRITIS ASSOCIATED WITH LIVER CIRRHOSIS

The glomerular changes of 50 autopsy cases of liver cirrhosis of different etiologies, such as alcohol abuse, HB virus infection, and nonA–nonB virus infection, were studied by light, immunofluorescence and electron microscopy. The glomerular changes observed were as follows; membranoproliferative glomerulonephritis (MPGN) type 1 (7 cases), mild form or early stage of MPGN type 1 (7 cases), mesangial proliferative glomerulonephritis with sub–endothelial deposits (13 cases), and mesangial proliferative glomerulonephritis without subendothelial deposits (12 cases). These glomerular changes were frequently accompanied by predominant IgA deposition (78% of the immunofluorescence positive cases). Minimal glomerular changes without electron dense deposits were 11 cases, in which IgA was not present in the glomeruli. Thus, glomerulonephritis associated with liver cirrhosis has revealed a]spectrum'of glomerular changes from MPGN type 1 to mesangial proliferative glomerulonephritis with a common feature of predominant IgA deposition, despite various etiological factors of liver cirrhosis, such as alcohol abuse, hepatitis B virus infection, and nonA–nonB virus infection. A pathophysiological condition of liver cirrhosis, e.g. reduced phagocytic activity of the reticuloendothelial system of the cirrhotic liver, Is thought to be a major factor for development of these glomerular changes. The pathogenesis of IgA predominant glomerulonephritis associated with liver cirrhosis may be concerned in the pathogenesis of IgA nephropathy, which still remains to be clarified. ACTA PATHOL. JPN. 33: 333–346, 1983.     

Human serum mannose-binding lectin (MBL)-associated serine protease-1 (MASP-1): determination of levels in body fluids and identification of two forms in serum

We developed an ELISA for human serum MASP-1, a Cls-like serine protease which is known to function in C4 and C2 activation. We then determined MASP-1 levels in 1063 sera from normal Japanese subjects ranging in age from 3 to 100 years, as well as in certain body fluids using this assay. Individual serum MASP-1 levels ranged from 148 to 12–83 μg/ml, with a normal frequency distribution pattern. The arithmetic mean ± s.d. of MASP-1 levels in serum was 6–27 ± 185 μg/ml, whereas levels of MASP-1 in cerebrospinal fluid and in urine were almost undetectable. When the mean ± s.d. of serum MASP-1 was calculated for each age group (10 year range) and values were then compared, the age group consisting of 3–9-year-olds (7–54 ± l-39;μ/ml) was found to have the highest value. When MASP-1 was measured in cord blood, it was shown that levels were already as high as those of 3–9-year-olds. The serum MASP-1 level was found to be as strongly dependent on age as is the serum MBL level. MASP-1 and MBL are thought to play an active part in immunity in younger people. It was found that the serum level of MASP-1 was much higher than that of MBL, and the major portion of human serum MASP-1 appeared to exist in the circulation as a form unbound to MBL.     

Clinical effectiveness of steroid pulse therapy combined with tonsillectomy in patients with immunoglobulin A nephropathy presenting glomerular haematuria and minimal proteinuria

Aim: The effectiveness of steroid pulse therapy combined with tonsillectomy (ST) has been shown in immunoglobulin A nephropathy (IgAN) patients with moderate or severe urinary abnormalities. The present study aimed to clarify whether the effectiveness may be extrapolated to IgAN with minor urinary abnormalities, and whether the effectiveness may depend on the histological severity with minor urinary abnormalities. Methods: Data on 388 IgAN patients diagnosed by renal biopsies between 1987 and 2000 in Sendai Shakaihoken Hospital, who presented glomerular haematuria and minimal proteinuria (≤0.5 g/day) at baseline, were analyzed. Cox regression was used to examine associations between baseline use of ST and subsequent clinical remission (CR), defined as negative proteinuria by dipstick and urinary erythrocytes of less than 1/high‐power field. The instrumental variable method was also used to overcome confounding by treatment indication. Results: During a median follow up of 24 months, we observed 170 CR cases. Patients receiving ST were younger and showed a better case‐mix profile. Patients with ST had a significantly higher rate of CR than patients without tonsillectomy or steroid pulse in an unadjusted (hazard ratio (HR) = 5.51, 95% confidence interval (CI) = 3.33–9.12, P < 0.001) or adjusted Cox model (HR = 4.65, 95% CI = 2.43–8.88, P < 0.001). Less severe histological findings were substantially associated with higher CR rate in ST group. Adjusting for confounding by treatment indication showed an attenuated but still significant effect of ST (HR = 3.10, 95% CI = 2.02–4.77, P < 0.001). Conclusion: ST significantly increased the probability of CR in IgAN patients with glomerular haematuria and minimal proteinuria, and it was more effective in those with less severe histological findings.     

The Effect of Tamsulosin Treatment on Erectile Functions in Patients with Lower Urinary Tract Symptoms (LUTS) due to Benign Prostate Hyperplasia: Correlation between Improvement of LUTS and Erectile Function

Objectives: To evaluate the impact of tamsulosin treatment on erectile function in patients with lower urinary tract symptoms (LUTS). Methods: Seventy‐five patients with LUTS received tamsulosin 0.2 mg once daily for 3 months. Subjective efficacy was assessed by International Prostatic Symptom Score (IPSS) for LUTS and International Index for Erectile Function 5 (IIEF5) for erectile dysfunction (ED). Objective efficacy was assessed by prostate volume and urine flow rate. All measurements were performed at baseline and month 3. On the basis of IPSS ratio (month 3/baseline), the patients were classified into good responders (≤0.75) and poor responders (>0.75). Good responders to ED were defined as the patients who improved IIEF5 score 3 or more. Results: Seventy‐four subjects completed the study. IPSS score showed significant improvement, but IIEF5 score showed no significant change. Forty‐three patients (58%) were classified into good responders to LUTS. The baseline score of IIEF5 in the good responders was significantly higher than that in the poor responders. Negative correlation was recognized between IPSS ratio and baseline score of IIEF5. Nine patients (13%) were able to classify into good responders to ED, who had significantly smaller prostate volume and showed significantly lower IPSS ratio. Conclusions: The tamsulosin therapy for LUTS patients showed a significant improvement of LUTS, but no significant change of erectile functions. The better response to LUTS was seen in the milder ED patient. Tamsulosin therapy may be effective not only on LUTS but also on ED in the patients who have small prostate.